Local HIV epidemics in the Asia-Pacific region are frequently concentrated within key populations engaging in male-to-male sex, injection drug use, and sex work, and largely occur in low- and middle-income settings where concurrent acute and chronic infections (e.g., tuberculosis, hepatitis B and C) are common and associated with increased morbidity and mortality. The IeDEA Asia-Pacific Research Collaboration has established a network of 60 clinical centers and research partners in 13 South, Southeast, and East Asian countries and Australia, that is evaluating a range of factors driving the epidemic and HIV disease and treatment outcomes in order to better understand how changing global treatment guidelines are being implemented, and to inform clinical practice and policy. The overall scientific goal is to evaluate the impact of HIV disease, co-infections, co-morbidities, an antiretroviral therapy management on short- and long-term clinical and programmatic outcomes in the region, and compare them across the IeDEA global consortium. The research agenda relies on data from core adult and pediatric cohorts, and supplemental cohorts of adolescents and acutely infected men who have sex with men, as well as targeted sub-studies on co- infections, non-communicable diseases, cancers, and drug use. Analyses addressing the specific aims will examine short- and long-term outcomes along the treatment and retention cascade, including time to treatment initiation, tolerability and durability of antiretroviral regimens, loss to follow-up, treatment failure, drug resistance, and cancer risk. Outcomes will be disaggregated by age (e.g., children, adolescents, adults, older adults), sex, key affected populations, and country income levels. This will be complemented through sub- studies of incident sexually transmitted infections and HIV treatment adherence among those using amphetamine-type stimulants, co-infections with tuberculosis and viral hepatitis, and adolescent transition to adult care. Studies will be supported by robust data management and analysis infrastructure, which has facilitated the successful harmonization of intra-regional data definitions and methodologies across 13 countries, as well as with IeDEA as a global consortium. Data collection and analytical methods will expand to increase the generalizability and the scope of research, and will utilize innovative research tools, including mHealth applications, online data and surveys, and social media outreach. IeDEA Asia-Pacific follows a model of shared leadership that prioritizes the engagement of local investigators in the development and implementation of cohort concepts, thereby building capacity well beyond the central coordinating and data centers and enhancing the impact of the work. Successful implementation of these studies will inform local and regional HIV clinical management practices and programs, and add to global understanding of the epidemiology of HIV, co-infections, and associated health outcomes.